Progranulin (PGRN) is a multifunctional growth factor expressed in central nervous system. Although PGRN expression is regulated by various stressors, its precise role(s) and regulatory mechanism(s) remain elusive. In this study, we used HT22 cells to investigate the physiological implications of oxidative stress-induced PGRN expression and the regulation of PGRN expression by oxidative stress. We observed that p38 MAP kinase was activated upon the addition of H2O2, and a selective p38 MAP kinase inhibitor attenuated PGRN induction by H2O2. To explore the physiological role(s) of the PGRN induction, we first confirmed H2O2-dependent responses of HT22 cells and found that the length and number of neurites were increased by H2O2. Pgrn knockdown experiments suggested that these changes were mediated by H2O2-induced PGRN expression, at least in part. Overall, the results suggested that an increase in oxidative stress in HT22 cells induced PGRN expression via p38 MAP kinase pathway, thereby controlling neurite outgrowth.

中文翻译：

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过氧化氢诱导颗粒体蛋白前体表达，以控制 HT22 细胞中的神经突生长。


颗粒体蛋白前体（PGRN）是一种在中枢神经系统中表达的多功能生长因子。尽管 PGRN 表达受到各种应激源的调节，但其确切的作用和调节机制仍然难以捉摸。在本研究中，我们使用HT22细胞研究氧化应激诱导的PGRN表达的生理学意义以及氧化应激对PGRN表达的调节。我们观察到 p38 MAP 激酶在添加 H2O2 后被激活，并且选择性 p38 MAP 激酶抑制剂减弱了 H2O2 的 PGRN 诱导作用。为了探索 PGRN 诱导的生理作用，我们首先证实了 HT22 细胞的 H2O2 依赖性反应，并发现 H2O2 增加了神经突的长度和数量。 Pgrn 敲低实验表明，这些变化至少部分是由 H2O2 诱导的 PGRN 表达介导的。总体而言，结果表明 HT22 细胞中氧化应激的增加通过 p38 MAP 激酶途径诱导 PGRN 表达，从而控制神经突生长。